Nerve Physiology PDF

Nerve Physiology Assistant Professor Dr. Mona A. Hussain Physiology department FOM - PSU  Objectives 1- Define the resting membrane potential. 2- Explain how the resting membrane potential is generated. 3- Define the action potential. 4- List the phases of...

Nerve Physiology Assistant Professor Dr. Mona A. Hussain Physiology department FOM - PSU  Objectives 1- Define the resting membrane potential. 2- Explain how the resting membrane potential is generated. 3- Define the action potential. 4- List the phases of action potential. 5- Describe the ionic basis of each phase of the action potential.  a b 1- Neurons are the structural and functional units of the nervous system 2- are amitotic, losing their ability to divide, and therefore cannot be replaced if they are destroyed (in most circumstances). Neurons that can be replaced include the olfactory epithelium of the nose and certain regions of the hippocampus in the brain, which is involved in memory. 3- Nuclei are clusters of cell bodies in the CNS, whereas ganglia are clusters of cell bodies in the PNS. 4- All neuron cell bodies have processes that extend outward. These extensions are called dendrites and axons. 5-Dendrites, which may be numerous, receive electrochemical messages 6- Axons send out electrochemical messages. Each neuron usually has only one axon. 7-Bundles of axons constitute tracts inside CNS and nerves inside PNS. Structural Classification of Neurons  Structural Classification of Neurons Neurons are classified based on the number of processes that extend from their cell bodies. The three major structural categories of neurons are: 1- multipolar neurons They are the most common, and represents more than 99% of neurons in the human body. 2- bipolar neurons They are very rare in the body. They are located in the retinas of the eyes and in the nasal cavity. 3- unipolar neurons These neurons have a single short process extending from the cell body that divides into two branches that function more like a single axon. One branch of the more distal Peripheral process is associated with dendrites near a peripheral body part and the other branch (the central process) enters the brain or spinal cord. Functional classes of neurons  Introduction Neurons operate by generating electrical signals that move from one part of the cell to another part of the same cell or to neighboring cells. Generation and conduction of electrical signals  Basic principles of electricity The predominant solutes in the extracellular fluid are sodium and chloride ions. The intracellular fluid contains high concentrations of potassium ions and ionized nondiffusible molecules, particularly proteins with negatively charged side chains and phosphate compounds. Electrical phenomena resulting from the distribution of these charged particles occur at the cell’s plasma membrane. Charges of the same type repel each other and oppositely charged substances attract each other and will move toward each other if not separated by some barrier.  The Resting Membrane Potential (RMP) All cells under resting conditions have a potential difference across their plasma membranes, with the inside of the cell negatively charged with respect to the outside. This potential is the resting membrane potential. For example, if the intracellular fluid has an excess of negative charge and the potential difference across the membrane has a magnitude of 70 mV, we say that the membrane potential is –70 mV (inside relative to outside). Recording of RMP The asterisk indicates the moment the electrode entered the cell.  RMP The resting membrane potential exists because of a tiny excess of negative ions inside the cell and an excess of positive ions outside. The excess negative charges inside are electrically attracted to the excess positive charges outside the cell, and vice versa. Thus, the excess charges (ions) collect in a thin shell tight against the inner and outer surfaces of the plasma membrane, whereas the bulk of the intracellular and extracellular fluids remain neutral.  The magnitude of the resting membrane potential The magnitude of the resting membrane potential depends mainly on two factors: (1) differences in specific ion concentrations in the intracellular and extracellular fluids, and (2) differences in membrane permeabilities to the different ions, which reflect the number of open channels for the different ions in the plasma membrane.  1- Ionic Concentrations *Intracellular chloride concentration varies significantly between neurons due to differences in expression of membrane transporters and channels.  Continue Equilibrium Equilibrium potential for K potential for ions Na ions Membrane is permeable to K ions Membrane is permeable to Na only ions only  Equilibrium potential At the equilibrium potential for an ion, there is no net movement of the ion because the opposing fluxes are equal, and the potential will undergo no further change. The Nernst equation describes the equilibrium potential for any ion: where Eion = equilibrium potential for a particular ion, in mV Ci = intracellular concentration of the ion Co = extracellular concentration of the ion Z = the valence of the ion  The equilibrium potentials for sodium (ENa) and potassium (EK) are  Continue The resting potential is generated across the plasma membrane largely because of the movement of potassium out of the cell down its concentration gradient through open or so-called leak potassium channels, so that the inside of the cell becomes negative with respect to the outside.  Goldman-Hodgkin-Katz (GHK) equation When channels for more than one ion species are open in the membrane at the same time, the permeabilities and concentration gradients for all the ions must be considered when accounting for the membrane potential. GHK equation calculates the membrane potential considering the concentrations and permeabitities of K, Na and Cl ions NB: The contributions of sodium and potassium to the overall membrane potential are a function of their concentration gradients and relative permeabilities.  Roles of Na+/K+-ATPase pump Direct role: The Na+/K+-ATPase pumps actually move three sodium ions out of the cell for every two potassium ions that they bring in. This unequal transport of positive ions makes the inside of the cell more negative than it would be from ion diffusion alone. ( small contribution to the RMP )  Continue Indirect role: the pump always makes an essential indirect contribution to the membrane potential because it maintains the concentration gradients down which the ions diffuse to produce most of the charge separation that makes up the potential.  Action potential Transient changes in the membrane potential from its resting level produce electrical signals. These signals occur in two forms: I. Graded potentials and II. Action potentials. Graded potentials are important in signaling over short distances, whereas action potentials are the long distance signals of nerve and muscle membranes.  Definition of action potential (AP) 1- A brief large 2- all-or-none depolarization of the membrane, reversing polarity in neurons; 3- it has a threshold 4- refractory period and 5- is conducted without decrement.  AP Action potentials are large alterations in the membrane potential; the membrane potential may change 100 mV, from –70 to +30 mV, and then repolarize to its resting potential. Action potentials are generally very rapid (as brief as 1–4 milliseconds.) Nerve and muscle cells as well as some endocrine, immune, and reproductive cells have plasma membranes capable of producing action potentials. These membranes are called excitable membranes, and their ability to generate action potentials is known as excitability. All cells are capable of conducting graded potentials, only excitable membranes can conduct action potentials.  Polarized, Depolarize, repolarize and hyperpolarize The resting membrane potential, at –70 mV, is polarized. “Polarized” simply means that the outside and inside of a cell have a different net charge. The terms depolarize, repolarize, and hyperpolarize are used to describe the direction of changes in the membrane potential relative to the resting potential. The membrane is depolarized when its potential becomes less negative (closer to zero) than the resting level. Overshoot refers to a reversal of the membrane potential polarity—that is, when the inside of a cell becomes positive relative to the outside. When a membrane potential that has been depolarized returns toward the resting value, it is repolarizing. The membrane is hyperpolarized when the potential is more negative than the resting level. NB: The changes in membrane potential occur because of changes in the permeability of the cell membrane to ions. Continue  The ionic basis of the action potential Types of ions channels: 1. Chemically gated- channels 2. Mechanically gated- channels 3. Voltage gated- channels (Na and K channels) 4. Thermally gated- channels Na and K voltage-gated channels Phases and ionic bases Threshold potential & All-or-none behavior Action potentials either occur or they do not occur at all. Another way of saying this is that action potentials are all-or-none. ( Do you know ?Firing a gun is all-or-none ) Continue  Refractory Periods During the action potential, a second stimulus, no matter how strong, will not produce a second action potential. That region of the membrane is then said to be in its absolute refractory period (ARP). ‫الممانعة المطلقة‬ Ionic basis of ARP: voltage-gated sodium channels are either already open or have proceeded to the inactivated state. Following the absolute refractory period, there is an interval during which a second action potential can be produced, but only if the stimulus strength is considerably greater than usual. This is the relative refractory period (RRP), ‫الممانعة النسبية‬ Ionic basis of RRP The voltage-gated sodium channels have returned to a resting state, and some of the potassium channels that repolarized the membrane are still open  Factors that affect nerve excitability Cooling Warming Mechanical pressure Alkalinity Ischemia Hypoxia Catelectrotonous Acidity Anelectrotonus ECF Na ions Increase Excess CO2, Alcohol anesthetic drugs ECF K ions increase Decrease of ECF Na ions Decrease of ECF calcium Decrease of ECF K ions ions ECF Ca ions Increase  ELECTROTONIC POTENTIALS The electrotonic potentials are passive changes in potential as a result of subtraction or addition of charges in the outer side of the nerve membrane. Cathodal stimuli cause catelectrotonus (Negative currents) (less negativity of membrane potential) while anodal stimuli (Positive currents) cause anelectronus (more negativity of membrane potential) ) ‫هيبدأ فين ‪AP‬؟ و ليه؟ و هيمشي في أي اتجاه؟‬  Conduction of AP; 1- Contiguous conduction of Action Potential Unmyelinated nerve fiber Conduction of AP: 2- Saltatory conduction  Conduction of AP: 2- Saltatory conduction Myelinated nerve fiber  Factors affecting Speed of AP conduction 1- Myelination: a. Myelinated fibers conduct impulses about 50 times faster than unmyelinated fibers of comparable size. b. Conserves energy 2- Diameter of nerve fiber: When fiber diameter increases, the resistance to local current decreases. Thus, the larger the fiber diameter, the faster action potentials can be propagated. So Large myelinated fibers, such as those supplying skeletal muscles, can conduct action potentials at a velocity of up to 120 m/sec, compared with a conduction velocity of 0.7 m/sec in small unmyelinated fibers such as those supplying the digestive tract.  BIPHASIC ACTION POTENTIALS Both recording electrodes are on the outside of the nerve membrane. It is conventional to connect the leads in such a way that when the first electrode becomes negative relative to the second, an upward deflection is recorded. Therefore, the record shows an upward deflection followed by an isoelectric interval and then a downward deflection.  Compound action potential In a mixed nerve containing fibers of different diameters, recordings made at some distance from the point of stimulation show a complex AP showing many spikes. This multipeaked AP is called compound action potential. The first spike to arrive belongs to the fastest conducting Aa fibers; this is followed by Ab and Ad spikes. If group B and C fibers are also present, their spikes will also be seen.  Graded Potentials Definition: Graded potentials are changes in membrane potential that are confined to a relatively small region of the plasma membrane. They are called graded potentials simply because the magnitude of the potential change can vary (is “graded”). Graded potentials are given various names related to the location of the potential or the function they perform; (receptor potential, synaptic potential, and pacemaker potential).  Characters of graded potentials Depolarizing graded potentials can be produced when transient application of a chemical stimulus opens ion channels at a specific location. These channels close relatively quickly when the signal molecules dissociate and diffuse away. (a) Local current through ion channels depolarizes adjacent regions. (b) Different stimulus intensities result in different degrees of depolarization, and regions of the membrane more distant from a given stimulus are depolarized less.  Characters of graded potentials Graded potentials: (a) can be depolarizing or hyperpolarizing, (b) can vary in size, (c) are conducted decrementally. the flow of charge decreases as the distance from the site of origin of the graded potential increases.  Characters of graded potentials: Summation If additional stimuli occur before the graded potential has died away, these can be added to the depolarization from the first stimulus. This process, termed summation